Polypeptides that bound to IL-23 receptor and inhibit binding of IL-23 and cell signaling thereof
The present invention relates to novel linear and cyclic polypeptides that bind to IL-23 receptor and inhibit the binding of IL-23 to its corresponding receptor and cell signaling thereof. The novel polypeptides of the present invention has a core structure of WX 1 X 2 X 3 W, where W is tryptophan, and X 1 , X 2 and X 3 are amino acids, with the proviso that when one of X 1 , X 2 or X 3 is W, the remaining two of X 1 , X 2 or X 3 cannot be W. Preferred core structures include WVDYW or WQDYW. The present invention relates a composition containing the novel polypeptides (linear or cyclic), and use of same in inhibiting cell functions including production of IL-22 and IL-17F from immune cells as well as in treating IL-23 associated human diseases including, for example, inflammatory bowel diseases, psoriasis and Crohn's disease, ulcerative colitis and multiple sclerosis.
1. An isolated cyclic polypeptide consisting of an amino acid sequence selected from the group consisting of SEQ ID NO: 177, SEQ ID NO: 178 and SEQ ID NO: 179, wherein said isolated cyclic polypeptide inhibits binding of IL-23 to IL-23 receptor and inhibits IL-23-mediated cell signaling.
2. The isolated cyclic polypeptide of claim 1 , wherein said isolated cyclic polypeptide consisting of SEQ ID NO: 177.
3. The isolated cyclic polypeptide of claim 1 , wherein said isolated cyclic polypeptide consisting of SEQ ID NO: 178.
4. The isolated cyclic polypeptide of claim 1 , wherein said isolated cyclic polypeptide consisting of SEQ ID NO: 179.
5. A method of inhibiting production of IL-17F in a Th17 cell in a human, comprising the steps of:
a) providing a human Th17 cell in need of inhibiting production of IL-17F; and
b) exposing said Th17 cell to said isolated cyclic polypeptide of claim 1 .
6. The method of claim 5 , wherein said IL-17F is IL-17F protein.
7. The method of claim 5 , wherein said production of IL-17F is assayed by an ELISA.
8. A method of inhibiting production of IL-17F in a splenocyte in a human, comprising the steps of:
a) providing a human splenocyte in need of inhibiting production of IL-17F from said splenocyte; and
b) exposing said splenocyte to said isolated cyclic polypeptide of claim 1 .
9. The method of claim 8 , wherein said IL-17F is IL-17F mRNA.
10. The method of claim 8 , wherein said production of IL-17F is assayed by RT-PCR.
11. A method of inhibiting production of IL-22 from a mononuclear cell in a human, comprising the steps of:
a) providing a human mononuclear cell in need of inhibiting production of IL-22 from said mononuclear cell; and
b) exposing said mononuclear cell to said isolated cyclic polypeptide of claim 1 .
12. The method of claim 11 , wherein said IL-22 is IL-22 protein.
13. The method of claim 11 , wherein said production of IL-22 is assayed by an ELISA.